Thumbnail
Access Restriction
Open

Author Hiller, J. M. ♦ Simon, E. J.
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword BASIC BIOLOGICAL SCIENCES ♦ CENTRAL NERVOUS SYSTEM DEPRESSANTS ♦ CHEMICAL BONDS ♦ AFFINITY ♦ BIOCHEMISTRY ♦ BRAIN ♦ CELL MEMBRANES ♦ COMPARATIVE EVALUATIONS ♦ DENSITY ♦ ENKEPHALINS ♦ HIPPOCAMPUS ♦ HYPOTHALAMUS ♦ LIGANDS ♦ MORPHINE ♦ RATS ♦ THALAMUS ♦ TISSUE DISTRIBUTION ♦ TRACER TECHNIQUES ♦ TRITIUM COMPOUNDS ♦ ALKALOIDS ♦ ANALGESICS ♦ ANIMALS ♦ AUTONOMIC NERVOUS SYSTEM AGENTS ♦ BODY ♦ CELL CONSTITUENTS ♦ CENTRAL NERVOUS SYSTEM ♦ CHEMISTRY ♦ DISTRIBUTION ♦ DRUGS ♦ ENDORPHINS ♦ ISOTOPE APPLICATIONS ♦ LABELLED COMPOUNDS ♦ MAMMALS ♦ MEMBRANES ♦ NARCOTICS ♦ NERVOUS SYSTEM ♦ NEUROREGULATORS ♦ OPIUM ♦ ORGANIC COMPOUNDS ♦ ORGANS ♦ PEPTIDES ♦ PHYSICAL PROPERTIES ♦ POLYPEPTIDES ♦ PROTEINS ♦ RODENTS ♦ VERTEBRATES ♦ Biochemistry- Tracer Techniques
Abstract Binding of (/sup 3/H)(d)-N-allylnormetazocine ((/sup 3/H)(d)-NANM) to rat brain membranes is stereospecific, reversible, and saturable (Bmax . 260 fmol/mg of protein) and manifests moderately high affinity (Kd . 20 nM). The rank order of potency among opioidbenzomorphans and phencyclidine (PCP) analogs for competition for (/sup 3/H)(d)-NANM-binding sites is as follows: (d)-NANM . PCP-3-OH greater than (d)-cyclazocine greater than N-ethylphenylcyclohexylamine greater than PCP greater than (l)-cyclazocine . dextrorphan greater than (d/l)-ethylketocyclazocine greater than (d/l)-bremazocine greater than (1)-NANM greater than 1-phenylcyclohexylamine greater than levorphanol. Other opioid ligands, relatively selective for each of the types of opioid binding sites other than sigma, such as morphine (mu), H-Tyr-D-Ala(Me)Phe-NH-CH2-OH (mu), D-Ala2-D-Leu5-enkephalin (delta), tifluadom (kappa), and U 50488 (kappa) as well as etorphine and naloxone were all unable to compete with (/sup 3/H)(d)-NANM for specific binding even at a concentration of 1 microM. Regional distribution studies of (/sup 3/H)(d)-NANM-binding sites show high density in the hippocampus, thalamus, hypothalamus, and amygdala and low density in cerebellum and nonfrontal neocortex membranes of the rat brain. These binding sites are very sensitive to protein-modifying enzymes and reagents such as trypsin and N-ethylmaleimide and to heat denaturation. These results provide direct biochemical evidence for the existence of distinct (d)-NANM-binding sites in rat brain.
Educational Use Research
Learning Resource Type Article
Publisher Date 1985-01-01
Publisher Place United States
Journal Mol. Pharmacol.
Volume Number 27
Issue Number 1
Organization New York Univ. Medical Center, NY


Open content in new tab

   Open content in new tab